Broad-spectrum therapeutics for influenza are critically needed to address the problem of influenza pandemics, a major threat to the public health globally. We have proposed studies that aim at generating a novel class of fusion proteins capable of blocking infections by all strains of influenza viruses. Specifically, the fusion protein is composed of a protease inhibitor that inhibits activation of all influenza viruses and an anchoring domain that helps to enrich the drug and prolong the drug retention on the respiratory epithelium. In the proposed phase I study, we will generate this proteinase inhibitor and its fusion proteins, compare their functional activities in vitro and choose the best construct for phase II study.